title: Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal disorder.
abstract: BACKGROUND
  Both hepatitis C virus (HCV) and human immunodeficiency virus (HIV) penetrate the central nervous system. HIV-associated neuroretinal disorder (HIV-NRD), a visual impairment of reduced contrast sensitivity and reading ability, is associated with cytokine dysregulation and genetic polymorphisms in the anti-inflammatory interleukin 10 (IL-10) signaling pathway. We investigated associations between HCV and HIV-NRD and between HCV and single-nucleotide polymorphisms (SNPs) in the IL-10 receptor 1 (IL10R1) gene.
  
  
  METHODS
  Logistic and Cox regression analysis were used to analyze risk factors for HIV-NRD in 1576 HIV-positive patients who did not have an ocular opportunistic infection at enrollment. Median follow-up was 4.9 years (interquartile range, 2.4-8.8 years). Four IL10R1 SNPs were examined in a subset of 902 patients.
  
  
  RESULTS
  The group included 290 patients with chronic HCV infection, 74 with prior infection, and 1212 with no HCV markers. There were 244 prevalent cases of HIV-NRD and 263 incident cases (rate = 3.9/100 person-years). In models adjusted for demographics, HIV treatment and status, liver function, and immune status, both the prevalence and incidence of HIV-NRD were significantly higher in patients with chronic HCV infection (odds ratio = 1.54; 95% confidence interval [CI], 1.03-2.31 and hazard ratio = 1.62; 95% CI, 1.13-2.34, respectively), compared to patients with no HCV markers. Chronic HCV was associated with rs2228055 and 2 additional IL-10R1 SNPs expected to reduce IL-10 signaling. HIV-NRD was not significantly associated with these SNPs.
  
  
  CONCLUSIONS
  HCV is a possible risk factor for HIV-NRD. Genetic analysis suggests that alterations in the IL-10 signaling pathway may increase susceptibility to HIV-NRD and HCV infection. Inflammation may link HCV and HIV-NRD.
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Branch
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.forename: Mark L
authors.initials: ML
authors.lastname: Van Natta
authors.forename: Efe
authors.initials: E
authors.lastname: Sezgin
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Fishman
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Dieterich
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Meinert
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Jabs
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics / Q000821:virology*; D006526:Hepatitis C / Q000453:epidemiology / Q000235:genetics / Q000821:virology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D012164:Retinal Diseases / Q000453:epidemiology / Q000235:genetics / Q000821:virology*; D012307:Risk Factors; D015398:Signal Transduction; D014481:United States / Q000453:epidemiology
chemical_list: D053701:Receptors, Interleukin-10
keywords: AIDS; HIV-1; HIV-associated neuroretinal disorder; cytomegalovirus retinitis; hepatitis C virus